OBJECTIVES: 1. Optimal design of clinical trials for comparing two treatments for a given patient horizon to maximize the total benefit to all patients involved in both the trial period and the subsequent use of the chosen treatment. 2. Adaptive designs in regression and control for determining the optimal dosage of a drug to secure a desired mean response, when the nature of the regression of response on dosage is unknown. 3. Estimation of parameters in time series of dependent biomedical variables, with emphasis on robust methods. 4. Empirical Bayes estimation of both the individual members of the set of all unknown parameters and the mean of those parameters whose sample values exceed some fixed value, in order to determine the cut-off point above which treatment should be applied.